View source for 4b7e


==FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH CONSENSUS ANKYRIN REPEAT DOMAIN-LEU PEPTIDE (20-MER)==
<StructureSection load='4b7e' size='340' side='right'caption='[[4b7e]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4b7e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B7E FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b7e OCA], [https://pdbe.org/4b7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b7e RCSB], [https://www.ebi.ac.uk/pdbsum/4b7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b7e ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Substrate specificity: Biochemical and crystallographic analyses reveal the hypoxia-inducible factor hydroxylase (FIH) as being promiscuous with respect to the residues that it can hydroxylate in beta-position, which in addition to Asn, Asp, and His include Leu and Ser residues. The Ser substrate is oxidized to an epimeric beta-geminal diol product.

Substrate Selectivity Analyses of Factor Inhibiting Hypoxia-Inducible Factor.,Yang M, Hardy AP, Chowdhury R, Loik ND, Scotti JS, McCullagh JS, Claridge TD, McDonough MA, Ge W, Schofield CJ Angew Chem Int Ed Engl. 2013 Jan 7. doi: 10.1002/anie.201208046. PMID:23296631<ref>PMID:23296631</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4b7e" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor inhibiting HIF|Factor inhibiting HIF]]
*[[Hypoxia-Inducible factor 1 alpha inhibitor|Hypoxia-Inducible factor 1 alpha inhibitor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chowdhury R]]
[[Category: Ge W]]
[[Category: Schofield CJ]]